Argentatin C Analogues with Potential Antinociceptive Activity and Other Triterpenoid Constituents from the Aerial Parts of Parthenium incanum

Four new triterpenes,25-dehydroxy-25-methoxyargentatin C (1), 20S-hydroxyargentatin C (2), 20S-hydroxyisoargentatinC (3),and 24-epi-argentatin C (4), togetherwith 10 known triterpenes (5-14)were isolated from the aerial parts of Parthenium incanum. The structures of 1-4 were elucidatedby detailed analysis of their spectroscopic data, and the known compounds 5-14 were identified by comparison oftheir spectroscopic data with those reported. Since argentatin C (11) was found to exhibit antinociceptive activity by decreasingthe excitability of rat and macaque dorsal root ganglia (DRG) neurons, 11 and its new analogues 1-4 were evaluated for their ability to decrease the excitability ofrat DRG neurons. Of the argentatin C analogues tested, 25-dehydroxy-25-methoxyargentatinC (1) and 24-epi-argentatin C (4) decreased neuronal excitability in a manner comparableto 11. Preliminary structure-activity relationshipsfor the action potential-reducing effects of argentatin C (11) and its analogues 1-4, and theirpredicted binding sites in pain-relevant voltage-gated sodium andcalcium channels (VGSCs and VGCCs) in DRG neurons are presented.